Culture

PSYCHOLOGICAL HEALTH MAY BE IMPORTANT PREVENTION FACTOR FOR SUDDEN DEATH IN GENETIC HEART DISEASE

Media Contact: Vanessa McMains, Ph.D., vmcmain1@jhmi.edu

Studying mice modeling a human genetic disease that causes irregular heartbeats and can lead to sudden death, Johns Hopkins Medicine researchers have shown that emotional stress seems to promote symptoms of the disease and worsens its progression. The researchers say in their study, published Nov. 24, 2020, in the Journal of Clinical Medicine, that physicians and patients would be wise to focus together on good mental health -- in addition to traditional exercise avoidance -- to keep patients healthy and avoid triggering symptoms.

"There's much evidence that our body and mind are connected so that our psychological states can change the course of disease," says Jacopo Agrimi, Ph.D., a research fellow in the laboratory of Nazareno Paolocci, M.D., Ph.D., associate professor of medicine at the Johns Hopkins University School of Medicine. "Prolonged stress may be like putting fuel on the fire in someone with a chronic disease. So, we need to ensure that we are taking patients' quality of life and psychological wellness into account when managing their disease."

The Johns Hopkins Medicine research study was conceived when the researchers heard anecdotal reports from patients at a seminar held as part of the Johns Hopkins ARVC/D Program.

Arrhythmogenic right ventricular dysplasia (ARVD), also known as arrhythmogenic right ventricular cardiomyopathy (ARVC), is a genetic heart condition and a leading cause of sudden death among young athletes, but it can affect people of all ages and all activity levels. ARVC/D was one of the diseases modeled by the mice in the study.

"Patients often reported that when they heard their defibrillator charging -- which is needed to shock their heart beat back into normal rhythm when disrupted -- they would panic due to past experiences resulting from the pain and discomfort of a defibrillator discharge," says Stephen Chelko, Ph.D., an adjunct assistant professor of medicine at the Johns Hopkins University School of Medicine, as well as an assistant professor of biomedical sciences at Florida State University. "As a result, many people also reported waking up after the shock, hearing the defibrillator recharge and become panicked again, thus creating a viscous cycle."

These patient stories led Chelko and Agrimi to survey patients with these genetic heart diseases about their stress levels during annual clinical follow-ups. They found that those with higher levels of perceived psychosocial stress showed a strong correlation with clinical symptoms as measured by cardiac magnetic resonance imaging or electrocardiogram.

With this knowledge, the researchers then took mice with the second most common genetic mutation for arrhythmogenic cardiomyopathy and put half of the group in stressful situations by exposing them to large, aggressive and bullying mice for weeks.

Almost a third of the mice with the genetic heart condition and placed in the stressful situation died of sudden death compared with the mice with the heart problem in non-stressful situations. The researchers also observed that the stressed mice who remained alive showed more cardiac damage and more rapid disease progression.

"Genetic heart disease is stressful enough without adding psychological stress, with athletes having to give up exercise and participation in sports when they are diagnosed," says Chelko. "We need physicians to help patients navigate the disease and treat the whole condition, including the mental wellness aspect."

Chelko and Agrimi are available for interviews.

JOHNS HOPKINS MEDICINE RESEARCHERS INCREASE UNDERSTANDING OF PEANUT ALLERGIES IN INFANTS

Media Contact: Waun'Shae Blount, wblount1@jhmi.edu

Approximately 2%-3% of Americans are allergic to peanuts. Previous research studies have suggested that introduction of the peanut in the first year of life to infants highly likely to develop a peanut allergy reduces that risk by approximately 80%. However, the best method to safely do this is unclear. Now, a Johns Hopkins Medicine research team has conducted a study that shows which babies are most at risk for peanut allergy and which tests are best for diagnosing them.

The team's findings were reported in two papers in the Jan. 19, 2021, issue of the Journal of Allergy and Clinical Immunology. One paper identifies the likelihood of babies developing a peanut allergy, finding that older infants and ones with moderate-to-severe eczema are most at risk. The other paper compares diagnostic tests for detecting peanut allergy.

"Early introduction of peanut is important to prevent peanut allergy," says Corinne Keet, M.D., Ph.D., associate professor of pediatrics at the Johns Hopkins University School of Medicine. "Current recommendations are that infants with severe eczema be exposed to peanuts early in the first year of life, but also that they get testing before introducing to make sure that they are not already allergic."

"We wanted to know what the real risk for peanut allergy was in this group, and in other potential risk groups, and what tests would be best to use for screening," she explains.

Researchers enrolled 321 children, ages 4 months to 11 months, who had at least one of the following risk factors: a family history of peanut allergy, moderate or severe eczema, or another food allergy other than peanut. The average age of the infants was 7 months and 58% were males. As for racial and ethnic demographics, 74% were identified as white, 8% as Black, 7% as Asian and 12% as multiracial or another racial background. Of the 321, 195 had eczema, 201 had a sibling or parent with a peanut allergy and 59 had a personal history of a food allergy other than peanut. Infants who were enrolled had a skin prick test and blood testing for peanut allergy, and were fed peanuts under observation.

The researchers found that 18% of the infants with moderate to severe eczema were allergic before introducing peanut. They found that risk increased with the severity of eczema, and also increased with each month between 4 months and 11 months of age.

This, say the researchers, suggests that introducing infants with severe eczema to peanuts before they reach the age of 6 months is necessary to effectively prevent the allergy. In contrast, they found that only 1% of the infants who had siblings or parents with a peanut allergy but who did not have eczema had peanut allergy when evaluated. Therefore, the researchers suggest that these infants do not need testing before starting to eat peanut products.

When comparing tests to predict the risk for developing a peanut allergy, the researchers found that the standard tests for peanut allergy -- the peanut-specific IgE (looking for antibodies formed in response to the entire peanut) and the peanut skin prick test -- had high false positive rates. A more recent test that detects IgE specific to one component of the peanut called Ara h 2, rather than the whole peanut, provided a more accurate diagnosis. Current guidelines for diagnosing peanut allergies in infants may need to be modified to reflect these findings, the researchers say.

The researchers conclude that parents of infants with significant eczema should discuss peanut introduction with their pediatricians, with the goal of getting the child exposed to peanut-containing foods before 6 months of age.

Ongoing research by the Johns Hopkins Medicine team involves finding ways to deal with peanut allergies already developed in children, including treatments such as medications and immunotherapy. Clinical trials are planned, including one that will study children with multiple food allergies in order to test methods for treating the allergies all at once.

Keet is available for interviews.

JOHNS HOPKINS CHILDREN'S CENTER PEDIATRIC PATIENT BEATS BLUE BABY SYNDROME

Media Contact: Kim Polyniak, M.A., kpolyni1@jhmi.edu

When Chelsea Presock and David White learned they were expecting, they couldn't have been happier. Halfway into the pregnancy, however, they received shocking news: their little bundle of joy had a heart defect. They were referred to Johns Hopkins Children's Center (JHCC), and their unborn baby girl was diagnosed with a rare congenital heart abnormality called tetralogy of Fallot (TOF), as well as an absent pulmonary valve (the valve that keeps deoxygenated blood on its way to the lungs from backflowing into the heart).

A combination of four heart defects that can lead to lack of oxygen in the blood and reduced blood flow to the lungs, TOF can cause blue baby syndrome, a condition in which a baby's skin can turn blue, often at birth. However, with her absent pulmonary valve, Presock and White's unborn baby was experiencing a compression of the airways that could lead to insufficient levels of oxygen for survival. Fewer than 1% of babies with congenital heart disease have the same diagnosis.

In the early morning hours of Nov. 21, 2019, Presock went into labor. She and White made the three-hour drive from their home on Deal Island on Maryland's Eastern Shore to JHCC to ensure their baby received the critical care she needed. Their daughter, Navy, was welcomed into the world later that same day. When she was born, her lips and feet were blue, along with some of her fingers.

"We didn't know the seriousness of the situation until they rushed me to cut the umbilical cord," White says.

Navy was soon taken to the pediatric cardiac intensive care unit and placed on extracorporeal membrane oxygenation (ECMO), a system that provides heart-lung bypass support outside the baby's body.

"I've only had a moment with this child and thinking about the 'what if' of 'will I have to bury this child?' That was definitely the scariest," Presock recalls.

Though her condition is considered extremely rare, Navy is one of an estimated 1 million children in the United States with a congenital heart defect. According to the U.S. Centers for Disease Control and Prevention, about 40,000 babies each year are born with congenital heart defects.

Navy remained on ECMO for four days after she was born and suffered a mild stroke, which can be a complication from the bypass support system. "It's overwhelming to see all of the lines, the beeping and the medicine, but then you see all this care around her and it makes up for it," Presock says.

After she was removed from ECMO, Navy did well at first but soon she began to face other serious health concerns not related to her heart condition. She developed reflux and was unable to keep food down. She was diagnosed with necrotizing enterocolitis (NEC), a bacterial inflammation that can ultimately destroy the wall of the intestines. Navy was placed on intravenous antibiotics to fight the NEC and underwent abdominal surgery to treat her reflux so that she could eat.

Separate from these problems, Navy also had difficulty breathing. Lung scans showed that one of the lobes of her lungs was larger than the other. Doctors at JHCC performed a lobectomy, taking an enlarged lobe off her right lung.

Little Navy's journey into the world was profoundly challenging, and she remained in the hospital for two and a half months. Finally, she healed enough to go home and get bigger and stronger to prepare for eventual heart surgery. During this time, Navy also was routinely followed by JHCC doctors, including Bret Mettler, M.D., director of pediatric cardiac surgery and co-director of the Blalock-Taussig-Thomas Pediatric and Congenital Heart Center at JHCC.

Eight months later, in September 2020, Navy had open-heart surgery at JHCC to fix her TOF condition and absent pulmonary valve by closing the hole in her heart, moving her pulmonary arteries and making them smaller. The eight-hour operation was successful, and 10 days later, Navy left the hospital.

"Navy was a profoundly sick baby who faced many challenges at such a young age because of her unique heart condition and so many other serious health concerns," Mettler says. "She has come through everything amazingly well, and will be able to live a healthy life."

JHCC doctors continue to follow Navy, who is now 14 months old, because she could need another heart operation later in life. Her parents say that she's thriving, adding that Navy is sassy and loves peanut butter and jelly.

"I want her to be healthy and happy and have a full childhood," White says.

"Navy would not be here without Johns Hopkins Children's Center," Presock says. "The reason God put surgeons here is for people like Navy to be fixed."

Presock, White and Mettler are available for media interviews.

Leesburg, VA, February 17, 2021--According to an open-access article in ARRS' American Journal of Roentgenology (AJR), COVID-19-related disseminated leukoencephalopathy (CRDL) represents an important--albeit uncommon--differential consideration in patients with neurologic manifestations of coronavirus disease (COVID-19).

"Increasingly," wrote Colbey W. Freeman and colleagues from the University of Pennsylvania, "effects of COVID-19 on the brain are being reported, including acute necrotizing encephalopathy, infarcts, microhemorrhage, acute disseminated encephalomyelitis, and leukoencephalopathy."

Among the 2,820 patients with COVID-19 admitted to the authors' institution between March 1 and June 18, 2020, 59 (2.1%) underwent brain MRI. Three (5.1%) had known white matter lesions from multiple sclerosis, 23 (39.0%) had white matter lesions of small vessel ischemic disease, six (10.2%) had acute infarcts, four (6.8%) had subacute infarcts, four (6.8%) had chronic infarcts, one (1.7%) had abnormal basal ganglia signal from hypoxemia, two (3.4%) had microhemorrhage in association with chronic infarcts, and two (3.4%) had microhemorrhage associated with acute or subacute infarcts.

Six patients (10.2%; four women, two men; age range, 41-86 years) had neuroimaging findings suggestive of CRDL--"characterized by extensive confluent or multifocal white matter lesions (with characteristics and locations atypical for other causes), microhemorrhages, diffusion restriction, and enhancement," Freeman et al. explained. Hypertension (4/6, 66.7%) and type 2 diabetes mellitus (3/6, 50.0%) were common comorbidities.

Reiterating that no established criteria exist for defining CRDL, "our patients had white matter lesions atypical for other causes," as well as "involvement of the bilateral middle cerebellar peduncles and corpus callosum," the authors of this AJR article concluded.

Your morning cereal or oatmeal. The bread on your sandwich. The corn chips for your snack, and the cookies for dessert. Not one would be possible with the humblest of ingredients: the seed.

Seeds such as wheat, rice and corn directly provide about 70% of the calories eaten by people every day. And they ultimately provide nearly every morsel of food, either by providing feed for livestock or by being grown into fruits and vegetables. It's no overstatement to say that without seeds, civilization would be impossible.

But seeds need our help. They are under stress from climate change, and under pressure to feed a growing population.

Scores of dedicated scientists spend their careers working to improve seeds. They are using the latest scientific advances to make seeds larger, more nutritious, and more resilient to stress.

Rodomiro Ortiz studies how plant breeding can help meet these goals. His research was recently published in Crop Science, a journal of the Crop Science Society of America.

As the science behind seed improvements, plant breeding is the foundation for ensuring agriculture meets humanity's needs.

"The seeds generated from plant breeding have desired traits that allow increases in productivity, reduce human malnutrition, improve genetic diversity in ecosystems, and ensure sustainable food production under the specter of global warming," says Ortiz.

Classic plant breeding doesn't add in extra DNA like genetic engineering does. Instead, plant breeders cross plants that each have uniquely strong features to create a new plant with several beneficial traits. The same process has been used by farmers and scientists for thousands of years to make better crops.

But today, plant breeders have access to more information and more tools than ever. For example, the widespread use of DNA sequencing gives plant breeders huge troves of data about useful genes. By figuring out which genes give rise to which useful traits, plant breeders can develop new varieties of crops much more quickly.

"Genome-derived knowledge of seed biology can enhance crop productivity, to improve food and nutritional supply through plant breeding," says Ortiz.

But genes are only one piece of the puzzle. Scientists like Ortiz need to know how the plant grows and what it looks like. In the past, scientists might have been able to easily look and tell that one plant had, for example, larger seeds. But today, improving seeds requires ever greater detail.

Enter phenotyping, the science of measurement. A plant's phenotype is its entire expression of its genes in its environment. The height and color of the plant. Its seeds' weight and shape. Its tendency to resist or succumb to disease -- these are all the phenotype.

Capturing this information is time intensive. Some of these traits are impossible for humans to even see. And seeds in particular are so small, measuring them by hand is unrealistic. Technology comes to the rescue.

"Phenotyping seed traits is a major bottleneck to systematic analysis of seed variation," says Ortiz. "Advances in digital imaging technology can automatically measure a variety of shape parameters using high resolution images of seeds."

With these tools in hand, plant breeders can improve seeds and develop new crop varieties faster than ever. Ortiz envisions making seeds larger, so each one has more calories to feed people. Larger seeds can also help the next generation of crops quickly grow in the fields, ready to produce a big yield. And plant breeders are trying to make seed proteins more nutritious or the fats inside seeds stable enough to last on grocery store shelves for longer.

Each of those improvements mean stronger seeds, and better food, for more people. So with your next spoonful of chewy oatmeal, consider the humble seed -- and the advanced tech and know-how -- behind every bite.

Some of the planet's rarest metals - used in the manufacture of smartphones and other electrical equipment - are increasingly being found in everyday consumer plastics, according to new research.

Scientists from the University of Plymouth and University of Illinois at Urbana-Champaign tested a range of new and used products including children's toys, office equipment and cosmetic containers.

Through a number of detailed assessments, they examined levels of rare earth elements (REEs) but also quantities of bromine and antimony, used as flame retardants in electrical equipment and a sign of the presence of recycled electronic plastic.

The results showed one or more REEs were found in 24 of the 31 products tested, including items where unregulated recycling is prohibited such as single-use food packaging.

They were most commonly observed in samples containing bromine and antimony at levels insufficient to effect flame retardancy, but also found in plastics where those chemicals weren't present.

Having also been found in beached marine plastics, the study's authors have suggested there is evidence that REEs are ubiquitous and pervasive contaminants of both contemporary and historical consumer and environmental plastics.

The study, published in Science of the Total Environment, is the first to systematically investigate the full suite of REEs in a broad range of consumer plastics.

While they have previously been found in a variety of environments - including ground water, soils and the atmosphere - the study demonstrates the wide REE contamination of the "plastisphere" that does not appear to be related to a single source or activity.

Dr Andrew Turner, Associate Professor (Reader) in Environmental Sciences at the University of Plymouth and the study's lead author, said: "Rare earth elements have a variety of critical applications in modern electronic equipment because of their magnetic, phosphorescent and electrochemical properties. However, they are not deliberately added to plastic to serve any function. So their presence is more likely the result of incidental contamination during the mechanical separation and processing of recoverable components.

"The health impacts arising from chronic exposure to small quantities of these metals are unknown. But they have been found in greater levels in food and tap water and certain medicines, meaning plastics are unlikely to represent a significant vector of exposure to the general population. However, they could signify the presence of other more widely known and better-studied chemical additives and residues that are a cause for concern."

The research is the latest work by Dr Turner examining the presence of toxic substances within everyday consumer products, marine litter and the wider environment.

In May 2018, he showed that hazardous chemicals such as bromine, antimony and lead are finding their way into food-contact items and other everyday products because manufacturers are using recycled electrical equipment as a source of black plastic.

His work was part of a successful application by the University to earn the Queen's Anniversary Prize for Higher and Further Education for its pioneering research on microplastics pollution.

It also builds on previous work at the University, which saw scientists blend a smartphone to demonstrate quantities of rare or so-called 'conflict' elements in each product.

If B is better than A, and C is better than B, it follows by the transitive property that C is better than A. And, yet, this is not always the case. Every kid is familiar with the Rock-Paper-Scissors game--the epitome of nontransitivity in which there is no clear hierarchy among the three choices, despite each two-way interaction having a clear winner: Paper beats Rock, Scissors beats Paper, and Rock beats Scissors.

Evolution may be teeming with nontransitive interactions as well. While natural selection - the process by which organisms better adapted to their environments are more likely to survive and pass on their genes - can be observed over shorter time intervals, there is still debate about whether fitness gains accumulate over long evolutionary time scales. In other words, one might expect that successive adaptive events (like the two-way interactions of Rock-Paper-Scissors) would translate into a cumulative increase in fitness, resulting in the very latest generation always being more fit than its all of its genealogical ancestors. However, this turns out to not be true in every case.

The evolutionary process, then, includes what are known as nontransitive interactions, sometimes producing organisms that are less fit than its ancestors. Experimental demonstrations of such nontransitivity, however, have been lacking.

Until now. A group of scientists at Lehigh University led by Gregory Lang, associate professor in the Department of Biological Sciences, has recently provided empirical evidence that evolution can be nontransitive. Lang and his team identify a nontransitive evolutionary sequence through a 1,000-generation yeast evolution experiment. In the experiment, an evolved clone outcompetes a recent ancestor but loses in direct competition with a distant ancestor.

The nontransitivity in this case arose as a result of multilevel selection that involved adaptive changes in both the yeast nuclear genome and the genome of an intracellular RNA virus. The results, which provide experimental evidence that the continuous action of selection can give rise to organisms that are less fit compared to a distant ancestor, are described in an article published in eLife Journal today called "Adaptive evolution of nontransitive fitness in yeast" (DOI: 10.7554/eLife.62238).

This study confronts two common misconceptions about evolution, according to Lang. The first, he says, is that evolution is a linear "march of progress" where each organism along a line of descent is more fit than all those that came before it.

Lang and his colleagues set out to determine how nontransitivity arose along a particular line of genealogical descent. In their 1,000-generation yeast experiment, nontransitivity arose due to adaptation in the yeast nuclear genome combined with the stepwise deterioration of an intracellular virus. Initially the population produced a virally encoded toxin and was immune to the toxin. As the population adapted, it fixed the beneficial nuclear mutations as well as mutations within the intracellular viral population that resulted in loss of toxin production. Over time the more beneficial nuclear mutations fix, and selection in the viral population resulted in a loss of toxin immunity - since the toxin was no longer produced. When placed in competition against its distant ancestor, the 1,000-generation evolved population lost due to the toxin produced by the ancestor.

"Another misconception is that there is a single locus of selection," says Lang. "Multilevel selection--as its name implies--states that selection can act simultaneously on multiple levels of biological organization."

In the context of this experiment, multilevel selection was common, says Lang. "Selection acts across multiple levels of biological organization, from genes within a cell to individuals within a population. Selection at one level can impact fitness at another.

"In fact, when we expanded our study of host-virus genome evolution to additional populations, we found that nearly half of the approximately 140 populations we studied experienced multilevel selection, fixing adaptive mutations in both the nuclear and viral genomes," he adds.

"Laboratory evolution experiments have proven highly effective for studying evolutionary principles, yet this work is the first to document a non-transitive interaction and provide a mechanistic explanation," says co-author Sean W. Buskirk, an assistant professor at West Chester University who collaborated on the research when a postdoctoral student in Lang's lab. "Ultimately, the presence of a virus in the ancestor drastically impacts how the evolved yeast populations compete and interact with one another."

The work of co-author Alecia B. Rokes, at the time an undergraduate biology major at Lehigh, focused on competing two intracellular viruses inside yeast cells in what she terms her very own "virus fight club."

"I worked on competing two viruses within the yeast cells to see if either virus variant had an advantage over the other, thus leading to higher frequency and one virus outcompeting the other," says Rokes, now a graduate student in microbiology at the University of Pittsburgh. "It was amazing to be part of the process of elimination, persistence, and pure curiosity that went into figuring out what was actually going on in these populations."

By showing that nontransitive interactions can arise along a line of genealogical succession, the team's work has broad implications for the scientific community's understanding of evolutionary processes.

"It resolves what evolutionary biologist Stephen Jay Gould referred to as 'the paradox of the first tier,' which is the failure to identify broad patterns of progress over long evolutionary time scales, despite clear evidence of selection acting over successive short time intervals," says Lang. "In addition, it calls into doubt whether true fitness maxima exist and, more broadly, it implies that directionality and progress in evolution may be illusory."

There is no coat colour that distinguishes dingoes from dingo-dog hybrids, a study involving UNSW Sydney has found.

The Centre for Ecosystem Science research suggests that animals assumed to be dingo-dog hybrids based on their coat colour and culled may have been pure dingoes.

"We actually found pure dingoes that had a brindle, black and tan, patchy or sable coat colour," Dr Kylie Cairns, a conservation biologist from UNSW Sydney and co-author of the study said.

"So that's showing that really dingoes are much more variable than we think and seeing an animal with an odd coat colour doesn't immediately mean that it's a hybrid.

"Using coat colour to decide what animals should be culled is not a very good idea."

The study follows 2019 research by UNSW and collaborators which found that almost all wild dogs in NSW are dingoes or dingo-dominant hybrids, challenging the widely held view that pure dingoes are virtually extinct in the state.

In Australia, dingoes are typically believed to be ginger in colour, while unusual coat colours such as brindle (black and brown stripes) or sable (ginger with a black stripe along the spine) are widely put forward to be evidence of contemporary domestic dog hybridisation.

But the study, published in the Journal of Zoology, found that while 53 per cent of dingoes have a ginger coat colour, 9 per cent were sable, 11 per cent black and tan, 14 per cent brindle, 5 per cent black, 1 per cent white and 6 per cent were patchy (white with spots of ginger or black).

Researchers from UNSW, University of Sydney and University of Melbourne took part in the study.

They examined the relationship between coat colour and ancestry in wild dingoes by testing the genetic makeup of 1325 wild canids (animals belonging to the Canidae family, such as dingoes, domestic dogs and wolves) across south-eastern NSW.

About a quarter of the samples were dingoes with no evidence of domestic dog ancestry while around three-quarters were dingoes with some domestic dog ancestry.

They found that domestic dogs with no dingo ancestry are rare in the wild, representing less than 1.5 per cent of the population.

There was also no coat colour that could distinguish dingoes with or without dog ancestry from each other, or from domestic dogs.

"The widely held idea is that a dingo is ginger animal with white socks and a white tail tip," Michael Letnic, senior author of the paper and professor in conservation biology and ecosystem restoration at UNSW Science said.

"But a key finding of this work is that coat colour should not be used to assess ancestry in dingoes."

The researchers suggest that other features such as floppy ears or a broad snout shape could be used to identify feral domestic dogs or recent dingo-dog hybrids.

The researchers are planning to use updated genetic techniques to look at dingo ancestry across Australia to uncover the origin of some of the coat colours.

"We want to examine whether these coat colours are ancestral or came from dogs originally but have been present in the population for 100 and 200 years," Dr Cairns said.

"We are curious to see if coat colour is part of the natural selection and adaption in dingoes, or if there are other reasons for these coat colours.

"For example, the black coat colour in wolves came from dogs and is associated with increased immunity and so we want to look to see if there is a similar pattern in dingoes."

Read the study in Journal of Zoology.

San Antonio, Texas (February 15, 2020) - Researchers at the Southwest National Primate Research Center (SNPRC) at Texas Biomedical Research Institute (Texas Biomed) may have found a new pathway to treat and control tuberculosis (TB), the disease caused by Mycobacterium tuberculosis (Mtb). Using single-cell RNA sequencing (scRNAseq), a next-generation sequencing technology, scientists were able to further define the mechanisms that lead to TB infection and latency. Co-led by Deepak Kaushal, Ph.D., Director of the SNPRC, this is the first study that used scRNAseq to study TB in macaques in depth. Results from the study were published in Cell Host & Microbe.

"Single-cell RNAseq is a novel approach that has developed in the past three or four years. It's an approach that allows us to look at the immune response more granularly, in higher resolution," Dr. Kaushal explained. "We were able to identify an immune response to Mtb infection in single lung cells as the infection progressed to disease, in some cases, or was controlled in others."

The number of TB related deaths has decreased by 30% globally. However, according to the World Health Organization, 1.4 million people died from TB in 2019; the disease continues to be one of the top communicable diseases plaguing low-income countries. It's one of several diseases negatively impacted by COVID-19 due to the virus's impact on health systems worldwide. TB is primarily spread by a cough or sneeze from someone who is infected with the disease; however, people with latent TB are not contagious. The disease is both preventable and treatable, but latent TB can become active if disrupted by another invading infection, such as Human Immunodeficiency Virus (HIV) and drug resistance continues to be a major impediment.

The study highlighted that plasmacytoid dendritic cells, which sense infection in the body, overproduce Type I interferons. Plasmacytoid dendritic cells are immune cells sent out to stop a bacteria or virus from replicating or causing disease. However, an overproduction of interferons can also cause harm. In this study, scientists observed that the interferon response correlated with disease instead of control. This information is important to scientists developing TB therapeutics and vaccines. Modifications to therapeutic/vaccine formulas may be needed to address interferon signaling.

"When we have a more precise understanding of how an infection develops, that knowledge can lead us to identify new drugs or therapies to treat disease and improve vaccines," Dr. Kaushal said. "Although our findings decreased the gap in knowledge of TB disease and latent infection, there's still more we need to learn."

Ben-Gurion University Researchers Uncover a Catch-22 When It Comes to Social Media Online Support Groups and Privacy Concerns

BEER-SHEVA, Israel...February 16, 2021- People who seek support online social media groups may end up not getting the help they need due to privacy concerns, according to a new study by Ben-Gurion University of the Negev (BGU) and Gutenberg University in Sweden.

The new research, published in Social Media & Society, addresses the "Catch-22" challenges that face secure digital communities and their potential members, who, when faced with verifying their identity, may not join these groups for fear of sensitive issues becoming public.

"Social networks, and the technologies that support them, provide valuable tools for forming and maintaining connections that build social capital," says Dr. Daphna Yeshua-Katz of the BGU Department of Communication Studies. "While we don't dispute the benefits of these far-reaching communities, our findings reveal the problematic paradox caused by security concerns."

The researchers examined communications shared within support groups on several platforms, including eating disorder blogs, a fertility support forum for women, a Facebook group for bereaved parents, as well as WhatsApp groups for Israeli military veterans with post-traumatic stress disorder. After conducting in-depth interviews with dozens of community members and site managers, it became apparent that lack of anonymity and public visibility in social media platforms such as Facebook and WhatsApp can marginalize those who face social stigma.

For example, to gain access to their online social support groups, Facebook and WhatsApp algorithms force potential members to reveal aspects of their identity they may not wish to share, including real name, photo, profile, and phone number. Moreover, on Facebook, all users are required to disclose their list of friends and activities. These default settings may deter people who are not ready to reveal their identity.

"Online support communities must guard against imposters whose presence threatens a group's safe-haven," says Dr. Yeshua-Katz. "The challenge is to find a way to maintain community boundaries without going underground in a way that removes these groups from the public sphere and blocks access to those who need support."

The placement of a wet cotton pellet against Mineral Trioxide Aggregate (MTA) is often recommended to ensure the completion of its setting reaction. This study aimed to evaluate the setting behaviour of MTA Angelus and NeoMTA by comparing their hardness after placing them in dry and moist conditions.

A simulated open apex was created on 40 polyvinyl tubes. The apical 4 mm of the tubes was filled with the two materials, NeoMTA Plus (Avalon Biomed Inc. Bradenton, FL, USA) and MTA Angelus (Angelus, Londrina, PR, Brazil) (n=20 per group). Both groups were subdivided into two subgroups based on the dry and wet conditions (n=10 per group). A wet cotton pellet was placed above the two materials in the wet group, and the coronal segment was sealed using Type II Glass ionomer cement (GC corporation Tokyo, Japan). Gutta-percha was placed against the test materials in the dry group with the coronal segment sealed with amalgam. Samples were placed in an oasis soaked in phosphate-buffered saline for seven days in 100% humidity and at 37°C.

Microhardness was measured independently at 4 and 2 mm from the apex. Hardness was compared between materials and conditions, applying analysis of variance (a = .05). The presence of dry or wet conditions had no significant effect on material hardness. MTA Angelus showed significantly higher hardness values compared with NeoMTA Plus. The moisture of the periapical environment can compensate for the absence of a wet cotton pellet and is adequate for the setting of the materials.

The schools in Vietnam observe a phenomenon that almost all parents send their children to school using private vehicles, mostly motorcycles. The parents usually park their vehicle on streets outside the school gates which can cause serious congestion and chances of of traffic accidents.

This study aims to identify the factors affecting the picking up of pupils at primary school by analysing typical primary schools in Hanoi city. The researchers used the binary logistic regression model to determine the factors that influence the decision of picking up pupils and the waiting duration of parents. The behaviour of motorcyclists during the process was identified and studied in detail using the Kinovea software. Through the results the researchers found that, on the way back home, almost all the parents use motorbikes (89.15%) to pick up their children. During their waiting time (8.48 minutes on average), the parents did a lot of illegal parking activities on the streets which caused a lot of trouble, testing the other commuters, and created chances for potential accidents in front of the primary school entrance gate. Risky picking-up behaviours were observed in the research.

Based on the results, several traffic management measures have been proposed by the researchers to improve traffic safety and to reduce traffic congestion in front of school gates. In addition, the results of the study is expected to provide a useful reference for policymakers and authorities.

NASA, in collaboration with other leading space agencies, aims to send its first human missions to Mars in the early 2030s, while companies like SpaceX may do so even earlier. Astronauts on Mars will need oxygen, water, food, and other consumables. These will need to be sourced from Mars, because importing them from Earth would be impractical in the long term. In Frontiers in Microbiology, scientists show for the first time that Anabaena cyanobacteria can be grown with only local gases, water, and other nutrients and at low pressure. This makes it much easier to develop sustainable biological life support systems.

"Here we show that cyanobacteria can use gases available in the Martian atmosphere, at a low total pressure, as their source of carbon and nitrogen. Under these conditions, cyanobacteria kept their ability to grow in water containing only Mars-like dust and could still be used for feeding other microbes. This could help make long-term missions to Mars sustainable," says lead author Dr Cyprien Verseux, an astrobiologist who heads the Laboratory of Applied Space Microbiology at the Center of Applied Space Technology and Microgravity (ZARM) of the University of Bremen, Germany.

Low-pressure atmosphere

Cyanobacteria have long been targeted as candidates to drive biological life support on space missions, as all species produce oxygen through photosynthesis while some can fix atmospheric nitrogen into nutrients. A difficulty is that they cannot grow directly in the Martian atmosphere, where the total pressure is less than 1% of Earth's - 6 to 11 hPa, too low for the presence of liquid water - while the partial pressure of nitrogen gas - 0.2 to 0.3 hPa - is too low for their metabolism. But recreating an Earth-like atmosphere would be expensive: gases would need to be imported, while the culture system would need to be robust - hence, heavy to freight - to resist the pressure differences: "Think of a pressure cooker," Verseux says. So the researchers looked for a middle ground: an atmosphere close to Mars's which allows the cyanobacteria to grow well.

To find suitable atmospheric conditions, Verseux et al. developed a bioreactor called Atmos (for "Atmosphere Tester for Mars-bound Organic Systems"), in which cyanobacteria can be grown in artificial atmospheres at low pressure. Any input must come from the Red Planet itself: apart from nitrogen and carbon dioxide, gases abundant in the Martian atmosphere, and water which could be mined from ice, nutrients should come from "regolith", the dust covering Earth-like planets and moons. Martian regolith has been shown to be rich in nutrients such as phosphorus, sulphur, and calcium.

Anabaena: versatile cyanobacteria grown on Mars-like dust

Atmos has nine 1 L vessels made of glass and steel, each of which is sterile, heated, pressure-controlled, and digitally monitored, while the cultures inside are continuously stirred. The authors chose a strain of nitrogen-fixing cyanobacteria called Anabaena sp. PCC 7938, because preliminary tests showed that it would be particularly good at using Martian resources and helping to grow other organisms. Closely related species have been shown to be edible, suitable for genetic engineering, and able to form specialized dormant cells to survive harsh conditions.

Verseux and his colleagues first grew Anabaena for 10 days under a mixture of 96% nitrogen and 4% carbon dioxide at a pressure of 100 hPa - ten times lower than on Earth. The cyanobacteria grew as well as under ambient air. Then they tested the combination of the modified atmosphere with regolith. Because no regolith has ever been brought from Mars, they used a substrate developed by the University of Central Florida (called "Mars Global Simulant") instead to create a growth medium. As controls, Anabaena were grown in standard medium, either at ambient air or under the same low-pressure artificial atmosphere.

The cyanobacteria grew well under all conditions, including in regolith under the nitrogen- and carbon dioxide-rich mixture at low pressure. As expected, they grew faster on standard medium optimized for cyanobacteria than on Mars Global Simulant, under either atmosphere. But this is still a major success: while standard medium would need to be imported from Earth, regolith is ubiquitous on Mars. "We want to use as nutrients resources available on Mars, and only those," says Verseux.

Dried Anabaena biomass was ground, suspended in sterile water, filtered, and successfully used as a substrate for growing of E. coli bacteria, proving that sugars, amino acids, and other nutrients can be extracted from them to feed other bacteria, which are less hardy but tried-and-tested tools for biotechnology. For example, E. coli could be engineered more easily than Anabaena to produce some food products and medicines on Mars that Anabaena cannot.

The researchers conclude that nitrogen-fixing, oxygen-producing cyanobacteria can be efficiently grown on Mars at low pressure under controlled conditions, with exclusively local ingredients.

Further refinements in the pipeline

These results are an important advance. But the authors caution that further studies are necessary: "We want to go from this proof-of-concept to a system that can be used on Mars efficiently," Verseux says. They suggest fine-tuning the combination of pressure, carbon dioxide, and nitrogen optimal for growth, while testing other genera of cyanobacteria, perhaps genetically tailored for space missions. A cultivation system for Mars also needs to be designed:

"Our bioreactor, Atmos, is not the cultivation system we would use on Mars: it is meant to test, on Earth, the conditions we would provide there. But our results will help guide the design of a Martian cultivation system. For example, the lower pressure means that we can develop a more lightweight structure that is more easily freighted, as it won't have to withstand great differences between inside and outside," concludes Verseux.

Hydrogen peroxide is used as a disinfectant, after dilution in water, to treat wounds. It is widely used across the industry as an eco-friendly oxidizing agent for impurity removal from semiconductors, waste treatment, etc. Currently, it is mainly produced by the sequential hydrogenation and oxidation of anthraquinone (AQ). However, this process is not only energy intensive and requires large-scale facilities, but AQ is also toxic.

As an alternative to the AQ process, hydrogen peroxide direct synthesis from hydrogen (H2) and oxygen (O2) using a palladium (Pd) catalyst was proposed. However, the commercialization of the technology has been challenging becausethe amount of water (H2O) formed is more than hydrogen peroxide (H2O2) during the process.*

*In the case of the Pd catalyst, 40% of hydrogen peroxide and 60% of water were maximally produced.

The Korea Institute of Science and Technology (KIST) announced that a joint research team of Dr. Sang Soo Han and Dr. Donghun Kim (Computational Science Research Center), Dr. Seung Yong Lee (Materials Architecture Research Center), and Professor Kwan-Young Lee at Korea University (Korea University, President Jin Taek Chung) developed a platinum-gold alloy catalyst for hydrogen peroxide production based on a computer simulation. Hydrogen peroxide selectivity can be increased to 95% by using this catalyst, compared with only 30-40% for a palladium catalyst, which indicates that mostly hydrogen peroxide on the developed Pt-Au catalyst can be produced with a small amount of water.

The joint research team between KIST and Korea University developed a new type of Pt-Au alloyed nanoparticle catalyst. Although it is difficult to homogeniously mix Pt and Au to develop an alloyed catalyst due to the intrinsic immiscibility of the metals, the researchers could successfully synthesize nanoparticles in the form of alloys by forcibly reducing **precursors of Pt and Au. Also, using this method, the content of each metal particle could be controlled by adjusting the amount of precursors of Pt and Au.

**Precursor: a substance from which the final specific substances is obtained by metabolism or chemical reactions

Hydrogen peroxide can be produced anywhere without large equipment by simply injecting both hydrogen gas and oxygen gas into an aqueous solution using the catalyst developed by the researchers. Unlike the Pd catalyst, the catalyst developed by the joint researchers can produce hydrogen peroxide up to 95% even at ambient temperature (10 ?C) and atmospheric pressure (1 atm). In addition, a catalytic reaction can be maintained for longer than 8 h, resulting from the structural stability of the catalyst.

The researchers clearly established the crystal structure of Pt-Au alloy nanoparticles by performing additional computer simulations, which is difficult to solve using general material analysis techniques. Furthermore, the catalytic reaction mechanism via compuater simulations was proposed at the atomic level in which the reason why the catalytic performance for hydrogen peroxide production is increased iswith increasing Au content was also clarified.

Sang Soo Han, Head of the Center at KIST, said, "it is important that the developed catalysts provide an eco-friendly hydrogen peroxide production option that can be applied without any limitation of manufacturing sites. Therefore, commercialization for the hydrogen peroxide direct synthesis would be greatly accelerated by overcoming the limitation of Pd catalysts with the low selectivity" and "the time and cost for the development of novel catalysts, mainly explored through trial and error, could be considerably reduced through computer simulations".

INDIANAPOLIS -- Researchers from Regenstrief Institute and Indiana University School of Medicine have developed and validated a short questionnaire to help patients report symptoms and assist healthcare providers in assessing the severity of symptoms, and in monitoring and adjusting treatment accordingly.

The tool, called SymTrak-8, is a shorter version of the SymTrak-23. The questionnaire tracks symptoms such as pain, fatigue, sleep disturbance, memory problems, anxiety and depression in older adults, enabling clinicians to provide better care for the diseases causing the symptoms.

"These symptoms are commonly reported in primary care, but they can be a sign of a variety of different diseases, so tracking them is important," said Kurt Kroenke, M.D., a Regenstrief Institute research scientist and IU School of Medicine professor of medicine. "This shorter version of Symtrak provides the same insight as the 23-question tool, but is less burdensome to complete. It could be very useful in busy primary care settings, where time can be limited."

The symptoms tracked by the tool can greatly impact quality of life, and they often appear in clusters as a result of multiple chronic conditions.

"The Symtrak-8 and Symtrak-23 provide a more complete picture of overall wellbeing and symptom burden," said Patrick O. Monahan, PhD, Regenstrief affiliated scientist and professor of biostatistics at IU School of Medicine. "The sensitivity of the questionnaires can be a good barometer of the efficacy of treatments."

The SymTrak tool draws upon strengths of existing questionnaires such as the PHQ-9, GAD-7, and PHQ-15, as well as PROMIS® (Patient-Reported Outcomes Measurement Information System) and the Healthy Aging Brain Care-Monitor. It can be filled out by a patient or a caregiver.

"We are excited about the scalability of these tools," said Dr. Kroenke. "They are clinically practical and clinically applicable, and the option of a shorter and longer version provides more flexibility for clinicians."

"SymTrak-8 as a Brief Measure for Assessing Symptoms in Older Adults" was published in the Journal of General Internal Medicine online ahead of print. This work was supported by National Institute on Aging grant R01 AG043465.

Lesbian, gay and bisexual (LGB*) people are significantly more likely to have mental health conditions and report alcohol and drug misuse than heterosexual people - according to a new study led by UCL researchers in collaboration with the University of East Anglia and City, University of London.

The findings, published today in Psychological Medicine, come despite apparently more tolerant societal attitudes towards same-sex relationships.

Given this continued disparity, the report's authors are now calling for Government action to ensure equity in health and social care services. They highlight the need for improved awareness among health professionals to the mental health needs of sexual minority groups and are calling for policies that improve societal understanding, starting with encouraging schools to intervene earlier to encourage tolerant attitudes towards sexual minorities across the whole school community.

The research analysed data from the 2007 and 2014 Adult Psychiatric Morbidity Surveys** (APMS), which had a combined sample of 10,433 people in England aged 16-64.

The surveys are completed via face-to-face interviews and/or computer self-completion and contain data relating to sexual orientation, common mental disorders (CMD), hazardous alcohol use, and illicit drug use. Further information is collected on experiences of bullying and discrimination, religious identification and childhood sexual abuse.

In this analysis of 2007 and 2014 data the researchers found there had been no change (ie no improvement) between 2007 and 2014, with LGB people remaining at higher risk of poorer mental health when compared to heterosexuals.

The prevalence of depression and anxiety disorders among bisexual people was 40%, and for lesbian and gay people it was 28%, which was significantly higher than that for heterosexuals at 16%. Similarly, illicit drug use was highest among bisexual people, at 37%, while for lesbian and gay people it was 25% and heterosexuals, at 10.5%. Alcohol misuse was highest in lesbian and gay people, at 37%, compared with bisexual people at 31%, and heterosexuals, at 24%.

Researchers found evidence to suggest that exposure to bullying and discrimination may help explain the observed poorer mental health in lesbian women and gay men but not in bisexual people.

No evidence was found to support any apparent contribution of differences in religious affiliation or experiences of adversity such as childhood sexual abuse in the association between sexuality and mental health problems.

Lead author, Dr Alexandra Pitman (UCL Psychiatry), said: "What this study highlights is the significant and ongoing disparity in mental health between LGB people and heterosexual people, as evidenced by higher levels of mental health problems and alcohol and drug misuse.

"In order to reduce this persistent inequality in society, we must ensure that health and social care professionals are better trained to identify and care for the wellbeing and mental health needs of sexual minority groups, who are often made to feel invisible within national health systems.

"Furthermore, secondary schools must implement policies and practices that create supportive environments for sexual minority students, including providing (and actively promoting) access to a member of staff who is a designated minorities contact person, who students can talk to in confidence about experiences of discrimination, bullying, or mental health difficulties. Schools in the UK can also learn from positive experiences of Gay Straight Alliance (GSA) clubs in US high schools, where students benefit from access to a hub for socialising, support, and activism.

"More can also be also be done to implement anti-discrimination strategies and policies in health care institutions. This might include: the use of positive images of LGB people in health service marketing material; ensuring that equal opportunities statements include grounds of sexual orientation; taking a LGB-affirmative stance in psychotherapy (with implications for training of therapists); and training all professionals not to assume heterosexuality."

Senior author, Professor Michael King (UCL Psychiatry), said: "Our research shows that stigma and social exclusion on the basis of sexual orientation may be more subtle and enduring than we imagine. Despite greater public acceptance and legal changes to ensure equality, the lived experience of a proportion of LGB people remains negative. We would emphasise however that these data also show that the majority of LGB people have robust mental health and lead happy lives."

Co-author, Dr Joanna Semlyen (The University of East Anglia), said: "We know that sexual minorities are at increased risk of poor mental health than the heterosexual population. What this paper shows is that those inequalities did not change between the two study collection points of 2007 and 2014.

"This is really important because it shows that, despite some changes in societal attitudes, people who are lesbian, gay and bisexual continue to experience poor mental health.

"What we need to do now is not only continue to monitor health in sexual minority populations as standard but also to design studies to understand what causes these inequalities and develop interventions to reduce them."

Memorial Sloan Kettering Cancer Center (MSK) physicians and scientists presented new research at the 2021 American Society of Clinical Oncology Genitourinary Cancers Symposium held virtually February 11-13. Notably, MSK medical oncologist Robert Motzer, MD, presented encouraging data from a phase III randomized study that assessed two new treatment combinations as first-line treatments that may prolong survival in people with advanced kidney cancer. Dr. Motzer's findings were also published on February 13 in the New England Journal of Medicine.

In this large, international trial involving 200 sites across 20 countries, Dr. Motzer and a team of investigators evaluated two new regimens as first-line treatments for patients with advanced renal cell carcinoma (RCC) -- lenvatinib (Lenvima®) plus pembrolizumab (Keytruda®) and lenvatinib plus everolimus (Afinitor®) -- as compared with the current standard of care, sunitinib (Sutent®). They found that treatment with lenvatinib plus pembrolizumab was associated with significantly longer progression-free survival and a higher percentage of patients with an objective response versus sunitinib. Furthermore, results for overall survival were significantly longer in favor of lenvatinib plus pembrolizumab over sunitinib. Treatment with lenvatinib plus everolimus was also associated with a higher percentage of patients with an objective response and longer progression-free survival than sunitinib, but it did not have a significantly greater effect on overall survival.

"We are encouraged by all the data," said Dr. Motzer. "As physician-researchers, we consistently strive to provide our patients with the most effective therapies and give those with advanced disease more options. These results could lead to a change in the standard of care for these patients."

Dr. Motzer and colleagues concluded that lenvatinib plus pembrolizumab achieved significant improvements in progression-free survival, overall survival, and objective response rate versus sunitinib in the first-line treatment of patients with advanced renal cell carcinoma.

Continuing to Make Strides in Research for Kidney Cancer Patients

Cancer immunotherapy was born at MSK a little over a century ago. Since then, physician-scientists across MSK have led the effort to develop immune-based treatments for different types of cancer. MSK has been at the epicenter of discoveries in the field, and the institution's work is bringing exciting new treatment options to people around the world. MSK physicians have extensive experience using immunotherapy to treat people with melanoma, kidney cancer, lung cancer, and other cancers, as well as in handling immune-related side effects.

Despite available therapies for advanced metastatic kidney cancer, new options are needed to improve long-term disease control and patient survival. Without treatment, kidney cancer can be an aggressive disease. At the time of diagnosis, the cancer has already spread to other organs in approximately 30 percent of people, and about one-third of people whose disease is confined to the kidney will have a relapse. In 2021, it is estimated that over 73,000 new cases of RCC will be diagnosed and there will be nearly 15,000 deaths due to RCC in the United States -- and numbers are expected to rise significantly in the next decade.

"Over the years we have made very encouraging progress in our overall understanding and treatment of advanced kidney cancer; however, ongoing research is very crucial so we can give patients better treatment options to help manage their disease," said Dr. Motzer.